Sifting through thousands of ant genes typically isn't part of the job for University of Utah human geneticist Mark Yandell, Ph.D.
But software the associate professor and a colleague developed works so well in annotating, or finding, human genes, an international collaboration of scientists asked Yandell's help to make sense of the data as they sequenced the genomes of four ant species. Three of the genomes were published Jan. 31 in the Proceedings of the National Academies of Sciences and the fourth will be published Feb. 24 in Public Library of Science Genetics (PLOS), with Yandell as a co-author on all four studies.
The software that Yandell and Ian Korf of the University of California, Davis, Genome Center developed, called MAKER, is a computational method that "annotates" genes in DNA sequences, recording their locations and documenting their structures for downstream research applications.Â For those in basic science research in human genetics, physiology, evolutionary biology, and other areas, MAKER can make the task of finding genes considerably easier and faster. But it also is valuable for translational and clinical research, aiding the development of diagnostic devices for personalized medicine.
The software already is being used by scientists around the world.Â
"It used to require 10 to 15 Ph.D.-level computer scientists working for a year to annotate a genome," Yandell says. "Now you can do it on a laptop overnight."
Although the ant genome sequencing took place at different labs, all the annotation was done by Yandell's MAKER software, which greatly streamlined the work, according to Chris R. Smith, who co-led the red harvester ant project. "Doing the annotation for all of these projects with MAKER made great sense," Smith said, "because the whole process of predicting genes gets more efficient when the evidence used for predicting them is shared across all of the genomes."
A molecular biologist by training, Yandell was part of the Human Genome Project (HGP) as both a postdoctoral fellow at Washington University and then as lead scientist in charge of creating software to annotate the human genome for Celera Corp, a private company involved in the HGP, and at the Howard Hughes Medical Institute and the University of California, Berkeley. Following his experience with the HGP, he developed MAKER, in part, to give biomedical scientists who lack the computer science expertise the means to annotate genes and then distribute their results to the larger research community.
Yandell has made the program free to those who use it for academic research, but it must be licensed for private use.
The cost of genome sequencing has dropped dramatically from more than $1 billion for the Human Genome Project's initial sequencing of the entire human genome.
That project also required a multitude of scientists working 13 years to complete the endeavor.Â But technological improvements have greatly reduced the cost, and now the genome of a single human can be sequenced for $5,000 to $10,000 and that of a new species for about $100,000.
Once a genome is sequenced, however, researchers still must locate specific genes and mutations in order to understand their roles in an organism or to link them to diseases or other medical problems, and that's where MAKER is proving to be extraordinarily valuable in annotating genes in humans and other species.
Yandell, for example, recently was contacted by the government of South Africa to annotate the genome of a fungus, known as pitch canker, devastating that nation's pine forests and lumber industry.
In collaboration with the Wingfield lab at Pretoria University, Yandell and Carson Holt, a Ph.D candidate in his lab, provided comparative analyses between the genomes of the pitch canker fungus and the genomes of other fungi aimed at identifying the genes that allow it to infest trees. Holt is a co-author on the ant genome studies as well.
Another area where MAKER can have an impact on the lives of billions of people is in annotating the genomes of food crops such as corn, potatoes, and rice. Annotating genes is essential for modern crop breeding programs, according to Yandell.
"The amazing thing today is that sequencing has become so cheap, that genomes are being sequenced right and left; these days it's annotating these genomes that's proving the bottleneck, not the sequencing. We think MAKER can help enormously with this. We are overjoyed to see it being embraced so enthusiastically worldwide," says Yandell.